Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: a randomized controlled trial

Abstract

Context: Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI).

Objective: To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI.

Design, setting, and participants: Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients.

Intervention: A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting.

Main outcome measure: Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4).

Results: The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, -4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, -4.0% to 9.7%]; P = .67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P = .88).

Conclusion: Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival.

Trial registration: clinicaltrials.gov Identifier: NCT00316004.

Figure 1

Trial Enrollment Imputation analysis for 6-month neurologic outcome included all patients who received the intervention. Final completer analysis outcome data included all patients who received the intervention, defined as having the fluid connected to the intravenous line regardless of how much fluid was administered, and who completed 6-month follow-up. EMS indicates emergency medical system.

Figure 2

Six-Month Extended Glasgow Outcome Score by Treatment Group—Imputed and Completer Analyses The Extended Glasgow Outcome Scale (GOSE) is an 8-point scale (1=dead, 2=vegetative, 3=lower severe disability, 4=upper severe disability, 5=lower moderate disability, 6=upper moderate disability, 7=lower good recovery, 8=upper good recovery). Imputed analysis represents the results for the entire cohort who received the intervention, using multiple hot deck imputations (20 imputations) for missing 6-month GOSE data. Completer analysis represents data from all cases with complete 6-month outcome data, including those who discontinued intervention but received partial infusion of study fluid.